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Pure Appl. Chem. Vol. 73, No. 9, pp. 1459-1464 (2001)

Pure and Applied Chemistry

Vol. 73, Issue 9


New small-molecule tubulin inhibitors*

G. Bacher, T. Beckers, P. Emig, T. Klenner, B. Kutscher, and B. Nickel

ASTA Medica AG, Research & Development Oncology, Weismuellerstrasse 45, 60314 Frankfurt, Germany

Abstract: The variety of biological agents directed toward the tubulin system exceeds those acting on DNA, making it an important target for cancer chemotherapy. However, the complicated chemical structures and restricted access to the natural resources, in combination with the development of drug resistance, limit the first generation of natural products. Considerable efforts in the search and synthesis of new synthetic compounds, such as small molecular tubulin inhibitors, gave access to novel potential/promising drugs. Among these substances, two series of novel, easily accessible indole classes were identified as tubulin-destabilizing agents. Owing to the synthetic nature, potent in vitro and in vivo antitumoral activity, and efficacy against multidrug-resistant (MDR) tumors, D-24851 and D-64131 have significant potential in cancer treatment.

*Plenary lecture presented at the Hungarian-German-Italian-Polish Joint Meeting on Medicinal Chemistry, Budapest, Hungary, 2 –6 September 2001. Other presentations are published in this issue, pp. 1387-1509.

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